In the present work, the development and application of two HPLC methods enabling the semipreparative enantioresolution of 1-(biphenyl-3-yl)-2-(1H-imidazol-1-yl)ethanol (1) and 1-[4-[(4-bromobenzyl)oxy]phenyl]-2-(1H-imidazol-1-yl)ethanol (2), two among the most potent and selective heme oxygenase-1 (HO-1) inhibitors known, are described. During the optimization step, different chiral stationary phase (CSP) features were evaluated, especially focusing the attention on (1) the type (electron-donating and electron-withdrawing) and position of the substituents in the phenyl moiety; (2) the physical coating or covalent immobilization of the modified polymer chain. Additionally, the effect of different types and amount of alcohol in the normal-phase eluent as well as of the column temperature, were investigated. For compound 1, Lux Cellulose-1 CSP containing cellulose tris(3,5-dimethylphenylcarbamate) was identified as the optimal choice in combination with a mobile phase consisting of n-hexane/ethanol—85/15 (v/v). Conversely, for compound 2, Lux Cellulose-2 CSP containing the cellulose tris(3-chloro-4-methyl phenylcarbamate)-based chiral selector was identified as the optimal choice, running the analysis with a n-hexane/ethanol/2-propanol—80/15/5 (v/v/v) mobile phase.

中文翻译：

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Phenylethanolic-Azole Heme Oxygenase-1 Inhibitors 的实验室规模半制备对映拆分

在目前的工作中，两种 HPLC 方法的开发和应用能够实现 1-(联苯-3-基)-2-(1H-咪唑-1-基)乙醇 (1) 和 1-[4-[ (4-溴苄基) 氧基]苯基]-2-(1H-咪唑-1-基)乙醇 (2) 是已知的最有效和选择性的血红素加氧酶-1 (HO-1) 抑制剂中的两种。在优化步骤中，评估了不同的手性固定相 (CSP) 特征，特别关注 (1) 苯基部分中取代基的类型（给电子和吸电子）和位置；(2)改性聚合物链的物理包覆或共价固定。此外，还研究了正相洗脱液中不同类型和量的醇以及柱温的影响。对于化合物 1，含有三（3,5-二甲基苯基氨基甲酸酯）纤维素的 Lux Cellulose-1 CSP 与由正己烷/乙醇 - 85/15 (v/v) 组成的流动相组合被确定为最佳选择。相反，对于化合物 2，包含基于纤维素三（3-氯-4-甲基苯基氨基甲酸酯）的手性选择剂的 Lux Cellulose-2 CSP 被确定为最佳选择，使用正己烷/乙醇/2-丙醇进行分析—80/15/5 (v/v/v) 流动相。